TRANSNEURONAL SIGNALS FOR AFFERENT REGULATION

用于传入调节的跨神经元信号

• 批准号: 3461737
• 负责人: RICHARD L. HYSON
• 金额: $ 10.03万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3461737
• 关键词: acoustic nerve; afferent nerve; aminoacid; auditory nuclei; auditory pathways; autoradiography; brain stem; cell age; chickens; electrophysiology; electrostimulus; glutamate receptor; immunocytochemistry; inositol phosphates; microtubule associated protein; neural information processing; neural transmission; neuroanatomy; neurons; neuropharmacology; phospholipase A2; protein biosynthesis; protein kinase C; second messengers; synapses; tritium; tubulin

Afferent activity has been shown to regulate a number of properties of postsynaptic neurons. It is well known that afferent input regulates the electrical activity of postsynaptic neurons through the action of neurotransmitters. Afferent input, however, also regulates the metabolic activity of postsynaptic neurons, particularly early in development. The signals for this latter form of transneuronal regulation are not known. The brain stem auditory system of the chick has proven to be a useful system for investigation transneuronal regulation of cellular metabolism. Second-order auditory neurons in nucleus magnocellularis (NM, the cochlear nucleus) receive their sole excitatory input from the ipsilateral auditory nerve. Elimination of activity in the auditory nerve on one side of the brain has been shown to alter a number of properties of NM neurons. For example, after a couple of days, a portion of the neurons in NM die and the rest shrink in size. Early after the elimination of auditory nerve activity in young chicks, changes in metabolism in NM neurons have been observed. For example, within 1 hour, there is a dramatic decrease in protein synthesis by NM neurons on the ipsilateral side of the brain. Such changes in NM neurons structure and function, however, are not observed after elimination of auditory nerve activity in adult birds. The proposed experiments investigate the signals involved in the regulation of both the electrical activity and metabolic activity of NM neurons. These experiments will be carried out on both young (1-2 week old) and adult (1 year old) chickens. Regulation of electrical activity is investigated first by analyzing the anatomical distribution of different classes of excitatory amino acid receptors. The physiological effects of excitatory amino acids are then assessed by application of specific agonists and antagonists while recording intracellularly from NM neurons in an in vitro brain slice preparation. Metabolic regulation is investigated by assessing changes in protein synthesis in the in vitro slice preparation after various treatments. Unilateral stimulation of the auditory nerve in vitro has been shown to produce similar changes in protein synthesis as those observed in vivo. Application of specific agonists and antagonists will assess the relative roles of different types of excitatory amino acid receptors and second messenger systems in transneuronal regulation of brain stem auditory system, 2) an understanding of the signals responsible for the regulation of neuronal metabolism in this system and 3) an understanding of age-related differences which may account for the age- dependence in the sensitivity of neurons to alterations of afferent activity.

传入活动已经被证明调节了许多特性 突触后神经元。众所周知，传入输入调节着 突触后神经元的电活动 神经递质。然而，传入输入也调节新陈代谢。 突触后神经元的活动，特别是在发育早期。这个 后一种形式的跨神经元调节的信号尚不清楚。 小鸡的脑干听觉系统已被证明是有用的 细胞代谢的跨神经元调节研究系统。 大细胞核(NM)内的二级听神经元 核团)接受来自同侧听觉的唯一兴奋性输入 很有胆量。消除一侧听神经的活动 大脑已被证明可以改变NM神经元的许多特性。为 例如，几天后，NM的部分神经元死亡， 其余的都缩小了。早期消除听神经后 雏鸡的活动，NM神经元代谢的变化 观察到的。例如，在1小时内， 大脑同侧NM神经元的蛋白质合成。是这样的 然而，未观察到NM神经元结构和功能的变化 在成年鸟的听神经活动消除后。 拟议的实验研究了参与调控的信号。 NM神经元的电活动和代谢活动。 这些实验将在幼儿(1-2周大)和 成年(1岁)鸡。对电活动的监管是 首先通过分析不同物种的解剖分布进行调查 兴奋性氨基酸受体的分类。的生理效应 兴奋性氨基酸然后通过应用特定的 NM神经元细胞内记录的激动剂和拮抗剂 一种体外脑片制剂。新陈代谢调节研究 通过评估体外切片制备过程中蛋白质合成的变化 经过各种治疗后。单侧听神经刺激术 体外培养产生的蛋白质合成变化与 那些在体内观察到的。特异性激动剂和拮抗剂的应用 将评估不同类型的兴奋性氨基酸的相对作用 脑跨神经元调节中的受体和第二信使系统 主干听觉系统，2)对负责 该系统中神经元代谢的调节及3)An 理解与年龄有关的差异，这可能解释年龄- 神经元对传入神经变化敏感性的依赖性 活动。